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Article

Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma

1
Department of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
2
Department of Pathology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
3
Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Gastrointestinal Cancer Group Cologne (GCGC), University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(2), 451; https://doi.org/10.3390/cancers12020451
Received: 7 January 2020 / Revised: 6 February 2020 / Accepted: 11 February 2020 / Published: 14 February 2020
(This article belongs to the Special Issue Cancer Biomarkers)
Dickkopf-2 (DKK2) has been described as Wnt/beta-catenin pathway antagonist and its expression is mediated by micro RNA-221 (miRNA-221). So far, there is only limited data characterizing the role of DKK2 expression in esophageal cancer. A tissue micro array of 192 patients with esophageal adenocarcinoma was analyzed immunohistochemically for DKK2, miRNA-221 expression by RNA scope, and GATA6 amplification by fluorescence in-situ hybridization. The data was correlated with clinical, pathological and molecular data (TP53, HER2, c-myc, GATA6, PIK3CA, and KRAS amplifications). DKK2 expression was detectable in 21.7% and miRNA-221 expression in 33.5% of the patients. We observed no correlation between DKK2 or miRNA-221 expression and clinico-pathological data DKK2 expression was correlated with TP53 mutations and amplification of GATA6. We did not detect a survival difference in dependence of DKK2 for the total cohort, however, in patients without neoadjuvant treatment DKK2 expression correlated with a prolonged survival (median overall-survival 202 vs. 55 months, p = 0.012) which turned opposite in patients that underwent neoadjuvant treatment. High amounts of miRNA-221 were in trend associated with a prolonged overall-survival (p = 0.070). DKK2 as a Wnt antagonist is associated with prolonged survival in patients without neoadjuvant treatment and changes its prognostic value to the contrary in patients after neoadjuvant therapy. The modulatory effects of neoadjuvant treatment in connection with DKK2 expression are not fully understood, but when considering DKK2 as a tumor marker, it is necessary to see it in the context of neoadjuvant therapy. View Full-Text
Keywords: response prediction; DKK2; GATA6; EAC response prediction; DKK2; GATA6; EAC
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MDPI and ACS Style

Schiffmann, L.M.; Loeser, H.; Jacob, A.S.; Maus, M.; Fuchs, H.; Zhao, Y.; Tharun, L.; Essakly, A.; Iannos Damanakis, A.; Zander, T.; Büttner, R.; Schröder, W.; Bruns, C.; Quaas, A.; Gebauer, F. Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma. Cancers 2020, 12, 451. https://doi.org/10.3390/cancers12020451

AMA Style

Schiffmann LM, Loeser H, Jacob AS, Maus M, Fuchs H, Zhao Y, Tharun L, Essakly A, Iannos Damanakis A, Zander T, Büttner R, Schröder W, Bruns C, Quaas A, Gebauer F. Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma. Cancers. 2020; 12(2):451. https://doi.org/10.3390/cancers12020451

Chicago/Turabian Style

Schiffmann, Lars M., Heike Loeser, Anne S. Jacob, Martin Maus, Hans Fuchs, Yue Zhao, Lars Tharun, Ahlem Essakly, Alexander Iannos Damanakis, Thomas Zander, Reinhard Büttner, Wolfgang Schröder, Christiane Bruns, Alexander Quaas, and Florian Gebauer. 2020. "Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma" Cancers 12, no. 2: 451. https://doi.org/10.3390/cancers12020451

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